When one stops eating vitamin B-12 (cobalamins), one passes through fo
ur stages of negative cobalamin balance: serum depletion [low holotran
scobalamin II, ie, low vitamin B-12 on transcobalamin II (TCII)], cell
depletion (decreasing holohaptocorrin and low red cell vitamin B-12 c
oncentrations), biochemical deficiency (slowed DNA synthesis, elevated
serum homocysteine and methylmalonate concentrations), and, finally,
clinical deficiency (anemia). Serum vitamin B-12 is on two proteins: t
he circulating vitamin B-12 delivery protein, TCII, and the circulatin
g vitamin B-12 storage protein, haptocorrin. Because TCII is depleted
of vitamin B-12 within days after absorption stops, the best screening
test for early negative vitamin B-12 balance is a measurement of vita
min B-12 on TCII (holoTCII). HoloTCII falls below the bottom of its no
rmal range long before total serum vitamin B-12 (which is mainly vitam
in B-12 on haptocorrin) falls below the bottom of its normal range.